The DFCI-based ALL Consortia consist of a 9-institution pediatric group and 8-institution adult group. The[unreadable] pediatric consortium has conducted multi-institutional trials since 1981, whereas the adult program began in[unreadable] 2003 with the initiation of a pilot/feasibility protocol for patients > 18-50 years old. Upon completion of the[unreadable] adult pilot in 2005, we propose to initiate a common adult/pediatric clinical trial for patients age 1-50 years[unreadable] with de novo ALL, as well as to enroll patients with relapsed or refractory ALL in studies testing agents[unreadable] discovered and screened in Projects 1-5 in the context of "investigational windows". Our pediatric consortium[unreadable] has a well-established record of successfully conducting randomized clinical trials and performing detailed[unreadable] studies of chemotherapeutic pharmacokinetics, acute morbidities, and late effects, all in the context of[unreadable] extremely favorable event-free survival outcomes. Our clinical trials of newly diagnosed ALL have a[unreadable] common treatment philosophy based on intensive early therapy, with research focused on minimizing[unreadable] toxicities without compromising efficacy. In childhood ALL, we have demonstrated differences in[unreadable] cytotoxicity, pharmacokinetics, toxicity and efficacy of various asparaginase preparations. We have also[unreadable] made fundamental contributions to the characterization and prevention of doxorubicin cardiotoxicity and late[unreadable] occurring neuropsychological toxicity, and have extensively evaluated quantitative measures of quality of life[unreadable] outcomes. In addition to clinical trials in newly diagnosed patients (ages 1-50 years), we are committed to[unreadable] developing novel therapies, and continuing our investigations into the pathogenesis of[unreadable] ALL , as well as chemical genomic markers of disease variability and potential targets for future[unreadable] therapy. The combined pediatric and adult consortia will provide approximately 180 patients per[unreadable] year, thus enabling the unique age-unrestricted clinical and laboratory studies described in Projects 1-6.